Asynchronous (delayed-interval) delivery in multifetal gestations is a rare occurrence. Current literature is composed of isolated case reports or small series at single institutions. Consequently, the authors assume that reporting bias of favorable outcomes influences the literature regarding perinatal outcomes. Few maternal or fetal complications have been reported. The purpose of this study was to estimate the maternal and fetal morbidities associated with asynchronous multifetal delivery.
MATERIALS AND METHODS
Institutional review board approval was obtained from Carilion Health Systems (Roanoke, VA) and the University of Tennessee Health Science Center at Memphis (TN). Women with a multifetal delivery were identified by International Classification of Diseases, 9th Revision, Clinical Modification codes for twin and triplet gestations. Charts from all twin or triplet deliveries were reviewed by 2 of the authors (J.L. and L.L.) for active attempts at delayed interval delivery. Active attempt to delay delivery was defined as the use of tocolytics and/or cervical cerclage placement after second-trimester vaginal delivery of the first fetus. Data from second and third fetuses were analyzed as a group termed retained fetus(es). Latency was defined as time between delivery of the first fetus and of subsequent fetus(es). A neonatal survivor was defined as one discharged from the hospital. Retinopathy of prematurity included only those with stage III disease. The attending neonatologist defined respiratory distress syndrome. Bronchopulmonary dysplasia was defined as oxygen requirement for greater than 40 days of life and at discharge. Intraventricular hemorrhage was reported for grade 3 or 4 only. Data were analyzed with Statview (SAS Institute, Cary, NC). Parametric data were reported as mean and standard deviation while nonparametric data were reported as median and range. To review the literature, the PubMed database (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi) was searched for the terms “asynchronous delivery” and “delayed interval delivery”. Only articles in English were reviewed.
Between April 1, 1991, and March 30, 2003, there were 96,922 deliveries including 1,352 multifetal gestation deliveries at the 2 institutions. Fourteen cases of attempted delayed-interval delivery were identified. Two additional women who were offered asynchronous delivery but opted for immediate delivery were not included in data analysis. One additional case of asynchronous delivery attempted at 31 weeks was not included because of the advanced gestational age. The occurrence rate of asynchronous delivery was 0.14 per 1,000 births. Pregnancy characteristics are in Table 1. A summary of the cases is in Table 2. Second-trimester rupture of membranes was the etiology of delivery of the first fetus in 12 (86%) of 14 cases. By study design, cases were attempted during the second trimester (gestational age of 18–25 weeks). As 10 different perinatologists initiated the attempt at increasing latency, there were no standardized techniques or protocols used during attempts to increase latency. All women approached for consideration of delayed interval delivery had dichorionic or trichorionic placentas and were without signs of infection. All women received tocolysis and various intravenous antibiotics after delivery of the first fetus. After delivery of the first born, the umbilical cord was ligated with permanent suture and the placenta left in situ in all cases. Two of 3 attempts at emergent cerclage placement were able to be placed while one was not because of advanced cervical dilation. One patient was managed as an outpatient after a prolonged hospitalization. Median latency achieved was 2 days and ranged from less than 1 day to 70 days. The most common indication for delivery of the retained fetuses was progressive preterm labor. All retained fetuses from triplet gestations were born within 24 hours of each other (delivery of second- and third-born fetuses). In triplet gestations, attempts at delayed delivery occurred after delivery of first and in 1 case after the second born.
One first-born fetus survived but developed bronchopulmonary dysplasia and stage III retinopathy of prematurity. There were 19 retained fetuses, 2 died in utero, 10 died between birth and day 57 of life, and 7 survived until hospital discharge (37%, 95% confidence interval 16%, 62%). Six of 7 survivors had major sequelae from prematurity (Table 2). Therefore, 1 of 19 was discharged from the hospital without major sequela (5%; 95% confidence interval 0%, 25%). Maternal morbidity included 2 placental abruptions, 8 cases of infectious morbidity including a case of septic shock with multiorgan system failure. The case of septic shock (Table 2, case 12) occurred in a women with rupture of membranes, expulsion of the fetus at 18 weeks, a latency of 8 days and vaginal delivery of a previable retained fetus. The patient developed an antepartum fever. After delivery, she developed Escherichia coli bacteremia, acute renal failure, and adult respiratory distress syndrome. She underwent a total abdominal hysterectomy, slowly recovered, and was discharged to home after a 36-day hospital stay. Uterine histology demonstrated multiple mircoabscesses. There were no maternal deaths.
Asynchronous multifetal delivery is an uncommon clinical situation that should only be considered at previable or periviable gestational ages. Because there are numerous case reports and several small series in the literature describing isolated successes, we suspect the current literature represents significant reporting bias of favorable outcomes. The purpose of this study was to estimate the morbidities associated with attempts at delayed interval delivery. Because of the extreme premature gestational age, we suspected that perinatal outcomes would not be as successful as reported in the literature. In our series, the median latency was only 2 days, and few fetuses were retained for more than 7 days. Despite the universal use of antibiotics and tocolytics, preterm labor resulted in delivery soon after delivery of the first fetus in the majority of cases.
Perinatal survival for retained fetuses (7 [37%] of 19) in this trial is less than that reported by Kalchbrenner et al1 who report 7 (78%) 9 survivors, Porreco et al2 who reported 9 (82%) of 11 survivors, and Hamersley et al3 who reported 5 of 6 survivors. There are several reasons for this discrepancy. First, Porreco et al2 included attempts at delayed delivery in the third trimester. Our series included only second-trimester deliveries. Second, a standard approach including amniocentesis (except Hamersly et al3), antibiotics, tocolysis, and cervical cerclage was used in the above series.1,2 Although there was no standard approach in our series, all women received intravenous antibiotics and tocolytics while cervical cerclage was utilized less frequently. Lavery et al4 reviewed the literature regarding the use of cervical cerclage in asynchronous deliveries and concluded that cerclage placement increases latency compared with those managed without cerclage.
Our poor fetal survival data are consistent with that of Van Doorn et al5 who reported 15 cases of attempted delayed delivery in women with gestational ages between 18 and 30 weeks. Survival was related to gestational age at delivery of first fetus. There was 1 neonatal survivor in 8 cases in which the gestational age at delivery of the first fetus was less than 25 weeks. In an extended report of the series by Porreco et al,2 Farkouh et al6 reported 20 cases of second-trimester delayed-interval delivery using the same standardized protocol as in the original series. Eight (44%) of 18 retained fetuses at a first-birth gestational age of less than 24 weeks survived. There were no cases of occult intra-amniotic infection discovered by amniocentesis. Neonatal morbidity was not reported.
In our series, perinatal outcome was dismal. Nearly all survivors developed significant morbidities often associated with long-term disabilities, such as grade 3 and intravenously intraventricular hemorrhage, stage III retinopathy of prematurity, and bronchopulmonary dysplasia. The literature contains a paucity of data regarding long-term follow-up on children born after delayed-interval delivery. Frauke et al7 report long-term (11 months-6 years) outcomes of retained fetuses. Significant psychomotor delay was present in 2 of 5 infants.
Maternal morbidity in our series included high rates of cesarean delivery, puerperal infection, and placental abruption. Infectious morbidity occurred in the majority of patients. With one exception, treatment with intravenous antibiotics was limited to a few days. One woman survived life-threatening sepsis.
Interpretation of our data has several limitations. Because asynchronous delivery is a rare event, the absolute number of cases reported is small. As cases were collected over a 12-year period of time, improvements in perinatal care may have an impact on outcomes in current pregnancies.
Women who are candidates for attempted asynchronous delivery should be informed of the high rate of perinatal morbidity and mortality. Attempts at delayed interval delivery are usually not successful at prolonging pregnancy for more than a few days. However, delayed delivery often results in an infant with severe morbidities instead of an infant born at a previable gestational age who would die soon after delivery. Counseling should include maternal risks of prolonged hospitalization as well as high rates of cesarean delivery, placental abruption, and puerperal infection. When associated with asynchronous delivery, puerperal infection is usually, but not always, easily treated with a few days of intravenous antibiotics.
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